Voclosporin (VCS, ISA247) is a novel calcineurin inhibitor (CNi), developed using a pharmacodynamic approach for use in solid organ transplantation and autoimmune disease.  CNi’s are the cornerstone of transplant immunosuppression.



The addition of one carbon molecule at the amino acid- 1 residue of cyclosporine (CsA) enhances binding of the VCS–cyclophilin complex to calcineurin and leads to faster elimination of the major metabolites of VCS. This results in an increase in potency and a lower drug and metabolite load leading to a more consistent pharmacokinetic–pharmacodynamic (PK/PD) relationship and enhanced calcineurin inhibition (CNi) compared with cyclosporine.

A previous Phase 2a conversion study in stable renal transplant patients has confirmed efficacy and tolerability of VCS.  A recent Phase 2b study in de novo  kidney transplant patients (the PROMISE study) demonstrated[1] that:

• VCS is as efficacious as tacrolimus in preventing acute rejection
  • Acute rejection rates were comparable to recent studies utilizing novel immunosuppressants.
• There was a clear relationship between VCS exposure, calcineurin inhibition and risk of acute rejection.
• Excellent renal function was demonstrated in all treatment groups with eGFR close to 70 mL/min.
• VCS is potentially associated with a reduced incidence of NODAT.